The purpose of this study was to evaluate the effect of age and the role of
cholecystokinin therapy on
gallstone formation in guinea pigs. Guinea pigs (31 1-mo-old, 31 1-yr-old, and 23 3-yr-old) were placed on a cholelithogenic diet for 2 wk while another 10 guinea pigs of each age group remained on regular chow. Half of each group received a daily injection of
cholecystokinin (0.5 nmol/kg). After 2 wk, guinea pigs were killed and the gallbladders were examined for
gallstones. The concentrations of bile constituents were determined. The prevalence of
gallstones was: 1-mo-old, control 0 out of 16,
cholecystokinin 1 out of 15; 1-yr-old, control 3 out of 14,
cholecystokinin 5 out of 16; 3-yr-old, control 10 out of 11,
cholecystokinin 3 out of 8.
Gallstone formation was significantly greater in 3-yr-old controls than in the two younger control groups, and
cholecystokinin treatment significantly reduced the incidence of
gallstones to near the level seen in younger guinea pigs. In the two younger age groups (but not in the 3-yr-old group), the cholelithogenic diet significantly reduced the concentration of
bile salts in bile below that of guinea pigs on a normal diet. The cholelithogenic diet and treatment with
cholecystokinin did not alter the relative compositions of bile
lipids from that of guinea pigs on a normal diet in any of the three ages studied. In the second experiment we measured gallbladder emptying in response to exogenous infusion of cholecystokinin-8 (100 fmol/kg/h-100 nmol/kg/h) in the same three age groups of guinea pigs in vivo that had been maintained on regular chow. There was no difference in
cholecystokinin sensitivity between the two younger age groups, but both were significantly more sensitive to
cholecystokinin than the 3-yr-old guinea pigs in rate of gallbladder emptying in the dose range 1 pmol/kg/h-1 nmol/kg/h. We conclude that a major factor in the increased incidence of
gallstone formation in the aged guinea pig
gallstone model is decreased gallbladder emptying due to decreased gallbladder sensitivity to
cholecystokinin.